Biochemistry Online: An Approach Based on Chemical Logic

Biochemistry Online

CHAPTER 2 - PROTEIN STRUCTURE

F: THERMODYNAMICS AND IMFs IN PROTEIN STABILITY

BIOCHEMISTRY - DR. JAKUBOWSKI

Last Update:  3/2/16

Learning Goals/Objectives for Chapter 2F:  After class and this reading, students will be able to ...

  • Differentiate between general charge and specific ion-ion pairs and summarize their role in protein stability
  • Draw the structure of N-methylacetamide  (NMA) and explain why it is a useful small molecule model to study the role of H bonds in protein stability
  • Draw a thermodynamics cycle for the transfer of a hydrogen bonded dimer of NMA from water to a nonpolar environment.  From the DG0 for steps in the cycle, and extending this model to protein, predict if buried H bond formation drives protein folding
  • Explain if studies of low temperature protein denaturation, high temperature protein, and DGo transfer of nonpolar side chains from water to more nonpolar solvents support the hydrophobic effect in protein stability
  • summarize the relationship between the empirical Hofmeister series and preferential binding of reagents into the hydration sphere of protein to explain the effects of denaturants (urea, guanidine salts) and stabilizers (glycerol, ammonium sulfate) on proteins

  • Using benzene solubility in water as a model to study the role of hydrophobic effect in protein unfolding and by inference in protein stability, interpret graphs of DG0, DH0, DS0 and DCp for the transfer of benzene to water, as a function of temperature.

  • from the above graph, explain if trends in the thermodynamic parameters for benzene transfer into water predict the observed protein unfolding/stability behavior of proteins as a function of temperature?

  • Give a molecular interpretation of the observed DCp for the transfer of nonpolar molecules into water.

  • Describe chain conformational entropy, relate it to conformational changes in acyl side chains in single and double chain amphiphiles with temperatures, and describe it role in protein stability.

  • state which of several given explanations for the observed destabilizing effects of Asn to Ala mutations in protein account for those observation

  • summarize graphically the magnitude and direction of the major contributors (inter- and intramolecular forces and effects) to protein stability

F11.  General Links and References

  1.  Bartlett, G. et al. n to pi* interactions in protein. Nature Chemical Biology. 6, pg 615 (2010).
  2. Pace, C. et al. Protein Ionizable Groups:  pK values and Their Contribution to Protein Stability and Solubility.  J. Biol Chem.  284, 13285 (2009)
  3. Silverstein, T.  Hydrophobic Effect:  J. Chem Ed.  85.  917-918 (2008)
  4. Sharp, K. & Madan, B. Hydrophobic Effect, Water Structure, and Heat Capacity Changes.  J. Phys.Chem. 101, 4343 (1997)
  5. Berezovsky, I & Shakhnovich, E. Physics and Evolution of Thermophilic Adaptation. PNAS 102, 12742 (2005)
  6. Beeby et al. The genomics of disulfide bonding and protein stabilization in themophiles.  PLoS Biology. 3, 1549 (2005)
  7. Courtenay, E. et al. Thermodynamics of interactions of urea and guanidinium salts with protein surfaces: relationship between solute effects on protein processes and charges in water-accessible surface area.  Protein Science. 10, 2485 (2001)
  8. Korkrgian, A. et al. Computational Thermostabilzation of an Enzyme.  Science. 308, pg 857 (2005)
  9. Kashefi, K. and Lovley, D. Extending the Upper Temperature Limit for Life.  Science. 301, pg 934 (2003).
  10. Omta et al. Negligible Effect of Ions on the Hydrogen-bond structure in liquid water.  Science, g 347, 320 (2003)
  11. Dixit et al. Molecular degregation observed in a concentrated alcohol-water solution. Nature. 416, pg 829 (2002)
  12. Pace, C.N. Polar Group Burial Contributes More to Protein Stability than Nonpolar Group Burial.  Biochemistry. 40, pg 310 (2001)
  13. Water at the Nanoscale (How water enters a hydrophobic nanotube - a molecular dynamics simulation) . Nature. 294414, pg 156, 188 (2001)
  14. Shortle & Ackerman. Persistence of Native-Like Topology in a Denatured Protein in 8 M Urea. Science. 293. pg 487 (2001)
  15. Brooks et al. Taking a Walk on a Landscape (about protein foldiing) Science, 293, pg 612 (2001)
  16. Chemistry Beyond the Molecule (supramolecular chemistry). Nature. 412, pg 397 (2001)
  17. Fernandez-Lopez et al. Rings of Destruction. (Cyclic peptides as drugs). Nature. 412 pg 392,  452 (2001)
  18. Scatena et al. Water at Hydrophobic Surfaces: Weak Hydrogren Bonding and Strong Orientation Effects. Science. 292. pg 908 (2001)
  19. Maritan et al. Best Packing in Proteins and DNA. Nature, 406, pg 251, 287 (2000)
  20. Oh et al. Folding-Driven synthesis of oligomers. Nature. 414, pg 889 (2001)
  21. Molecules at the Edge (solvent interactions at interfaces) Nature. 410, pg 645 (2001)
  22. Oesterhelt et al.  Unraveling a membrane protein (denaturing a protein with atomic force microscopy). Science. 288, pg 63, 143 (2000)
  23. Sohl et al. Unfolded conformations of a-lytic protease are more stable that its native state.  (has large kinetic barrier to unfolding). Nature. 395, pg 817 (1998)
  24. Pascher et al. Protein folding triggered by electron transfer. Science. 271, pg 1558 (1996)
  25. Koide et al. Design of a single-layer b-sheet without a hydrophobic core.  Nature. 403, pg 456 (2000)
  26. Nelson et al. Solvophobically driven folding of nonbiological oligomers.  Science. 277, pg 1793 (1997)
  27. Pace,C. N. et al. Forces contributing to the conformational stability of proteins. FASEB Jouranl. 10, 7583 (1996)

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